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A phase I study of vincristine, escalating doses of irinotecan, temozolomide and bevacizumab (VIT-B) in pediatric and adolescent patients with recurrent or refractory solid tumors of non-hematopoietic origin

A PHASE I STUDY OF VINCRISTINE, ESCALATING DOSES OF IRINOTECAN, TEMOZOLOMIDE AND BEVACIZUMAB (VIT-B) IN PEDIATRIC AND ADOLESCENT PATIENTS WITH RECURRENT OR REFRACTORY SOLID TUMORS OF NON-HEMATOPOIETIC ORIGIN
by
Rajkumar Venkatramani
___________________________________________________________________________
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CLINICAL AND BIOMEDICAL INVESTIGATIONS)
December 2010
Copyright 2010 Rajkumar Venkatramani

Vincristine, irinotecan and temozolomide have been used in various combinations to treat pediatric solid tumors. These combinations, in general have been well tolerated. Outcomes for patients with solid tumors who have been treated with various cytotoxic agents have reached a plateau over the last two decades, with similar responses in various resistant cancers. Incorporation of newer agents with different mechanisms of action with cytotoxic chemotherapy may improve response rates and outcomes. Recently several agents that target similar pathways in a broad range of cancers have become available. Only few of them have been tested in the pediatric population. Bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF) is one such agent. The novel combination of vincristine, irinotecan, temozolomide and bevacizumab with their unique mechanisms of action and non-overlapping dose limiting toxicity could be useful in refractory solid tumors. This phase I study is designed to determine the maximum tolerated dose of irinotecan given intravenous for 5 days every 3 weeks in combination with fixed doses of vincristine, temozolomide and bevacizumab (VIT-B).

A PHASE I STUDY OF VINCRISTINE, ESCALATING DOSES OF IRINOTECAN, TEMOZOLOMIDE AND BEVACIZUMAB (VIT-B) IN PEDIATRIC AND ADOLESCENT PATIENTS WITH RECURRENT OR REFRACTORY SOLID TUMORS OF NON-HEMATOPOIETIC ORIGIN
by
Rajkumar Venkatramani
___________________________________________________________________________
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CLINICAL AND BIOMEDICAL INVESTIGATIONS)
December 2010
Copyright 2010 Rajkumar Venkatramani